The goal of this project is to perform a detailed characterization of HLA variants in patients afflicted by multiple sclerosis (MS), neuromyelitis optica (NMO), myasthenia gravis (MG), Parkinson's disease (PD), and schizophrenia (SCZD), all neurological diseases with documented 6p21 genetic association signals. We will use a cost-effective and highly reproducible next-generation sequencing methodology, customized genotyping algorithms, and a multi-layered analytical approach to assess allelic and haplotypic associations with disease risk. Specific Aim 1 will develop and implement the methodologies for unambiguously genotyping the HLA-A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPA1 and DPB1 loci in patients and controls. Specific Aim 2 will characterize HLA noncoding polymorphisms and their association with neurological diseases, and enhance the study design through trans-ancestry analyses and the collaboration with Project 2 to identify relevant HLA-KIR interactions. This project is submitted as a key component of the larger INDIGO consortium effort. Central to immunity and critically important for human health, HLA molecules are encoded by complex genetic systems with extraordinarily high levels of sequence and structural variation and complex expression patterns. Characterization of HLA variation at high resolution will permit us to fully appreciate the impact of this diversity across a wide range of neurological diseases.